During the extracorporeal treatment of blood, a decrease in the patient's blood volume (BV) and, hence, of the patient's relative blood volume (RBV) takes place. Its decrease depends on a number of parameters such as the absolute blood volume (BV) at the beginning of the treatment, an ultrafiltration rate (UFR) applied, if applied, and the like. Patients who are treated at an ultrafiltration rate (UFR) that has been set (too) high are likely to collapse during, e. g., dialysis because of the amount of fluid withdrawn from their body by the treatment. Patients who are treated at an ultrafiltration rate (UFR) that has been set (too) low are likely to unnecessarily spend time at the treatment site (hospital, clinic or even at home bound to the treatment machine), or, worse, to be sent home again without having reduced their overhydration (OH) level to an appropriate extent.
By means of the present invention, a method for calculating or approximating a value representing the relative blood volume (RBV) at a certain point of time, or a value representing the refilling volume (V_refill) of a patient that may be observed or found during or due to a blood treatment of the patient and/or for predicting a relative blood volume (RBV) with regard to a future time point or an absolute blood volume (BV) for a future time point is suggested. Also, an apparatus for carrying out the method according to the present invention is provided, as well as a device comprising the apparatus, digital storage means, a computer program product, and a computer.
In one aspect of the present invention, the method for calculating or approximating or predicting a value representing the absolute or relative blood volume or a value representing the refilling volume or predicting a future value (like RBV_end) comprises the step of considering one or more calculated or measured value(s) reflecting an overhydration level of the patient or an approximation thereof.
The patient can be either a human being or an animal. The patient may be sound or ill. The patient may be in need of medical care or not.
In another aspect of the present invention, the apparatus is configured to carry out the method according to the present invention.
In another aspect of the present invention, the blood treatment device comprises at least one apparatus according to the present invention.
In another aspect of the present invention, the digital storage means, in particular a disc, CD or DVD, flash memory, USB memory, or the like has electrically readable control signals which are able to interact with a programmable computer system such that a method according to the present invention will be executed.
In another aspect of the present invention, the computer program product has a program code stored on a machine readable data medium for executing a method according to the present invention when executing the program product on a computer.
In another aspect of the present invention, the computer program has a program code for the execution of a method according to the present invention when executing the program on a computer.
Embodiments can include one or more of the following features.
In certain embodiments according to the present invention, a point of time falls within a particular blood treatment session. In some embodiments, a point of time is a time when a blood treatment session has just come to an end.
In some embodiments according to the present invention, observing or finding a value is to be understood as measuring the value, as calculating the value or as deriving or determining it from other values of other parameters having influence on the value in question.
In certain embodiments according to the present invention, a value measured, observed, calculated or determined “due to a blood treatment” means a value of a parameter that has been changed due to the blood treatment. The value itself may be measured, observed, calculated or determined during, before or after a blood treatment session.
In some embodiments according to the present invention, a blood treatment may be a hemofiltration, an ultrafiltration, and/or a hemodialysis method.
In certain embodiments according to the present invention, “considering” a value means taking the value into account, in particularly in a subsequent mathematic computation. This may take place by means of a mathematic formula referring to the considered value or comprising it or by establishing a mathematic relation between certain parameters or value including the “considered” one. In some embodiments according to the present invention, “considering” a value may be understood as using the value as an input value that is input into, for example, a (mathematic) formula, a computer, a control unit, a processor, or the like. The input value may originate from a measurement, a diagram, a spreadsheet, a table, or the like, for example.
In some embodiments according to the present invention, a value representing or reflecting a parameter, such as the absolute blood volume or the overhydration level of a patient, means either a value that directly or indirectly states or indicates that parameter. For example, in certain embodiments according to the present invention, a value representing or reflecting the overhydration of a patient may be “3” followed by the dimension “liter”, whereas a value that indirectly allows to derive or determine or approximate the overhydration of the patient may also be “3” having the dimension ‘kilogram’, or may be the abdominal girth, for example.
In some embodiments according to the present invention, a value representing or reflecting a parameter such as the absolute blood volume, the relative blood volume, the refilling volume or the overhydration of the patient is to be understood as the absolute blood volume, the relative blood volume, the refilling volume or the overhydration or as values thereof, e.g. noted in “liter”.
In certain embodiments according to the present invention, an overhydration “level” may be understood as the amplitude or the extend of the overhydration. Both the term “overhydration” and the term “overhydration level” may relate to absolute or to relative values. If understood as a relative value, “overhydration” may be related to the normohydrated state of the patient who does not need fluid removal and/or whose kidneys work in the way they do in sound people.
In some embodiments according to the present invention, the overhydration or overhydration level is defined as the difference between the weight of the patient who needs excess water removal due to kidney problems and the patient's dry-weight. The dry-weight may be the patient's weight in a condition where no excess fluid exists or where no excess fluid has to be removed. The patient's dry-weight may be defined as in WO 2006/002685 A1. The respective disclosure of WO 2006/002685 A1 is hereby incorporated by way of reference.
In certain embodiments according to the present invention, an overhydration and an overhydration level (whereby these terms may be used interchangeably in some embodiments according to the present invention) relate to an overhydration or overhydration value of the patient right before starting the blood treatment session, at the beginning thereof, or during the blood treatment session.
In some embodiments according to the present invention, the overhydration or the overhydration level of a patient means the water or excess fluid accumulated within the body which the skilled person understands as fluid that should be removed—in parts thereof or as a whole—by means of the blood treatment.
In certain embodiments according to the present invention, the overhydration or the overhydration level equals the water or excess fluid accumulated within the body that would have been removed from the body by the kidneys if the kidneys worked properly.
In some embodiments according the present invention, some or all of the method steps are carried out by means of corresponding devices such as one or more processors. The devices are adapted and/or configured for carrying out the respective method steps.
In certain embodiments according to the invention, the method is a computer-implemented method.
In some embodiments according to the invention, the method is an automatic dialysis method.
In some embodiments according to the present invention, the method is an operator independent method for calculating or approximating or predicting a value representing the absolute blood volume, the relative blood volume or the refilling volume, or for controlling a blood treatment device.
In certain embodiments, the method according to the present invention encompasses considering the absolute start blood volume upon or before beginning the blood treatment for calculating or approximating or predicting either a value representing the relative blood volume or a value representing the refilling volume.
In some embodiments, for assessing the absolute start blood volume, at least one value reflecting the lean mass and at least one value reflecting the fat mass of the patient's body, and/or approximations thereof, are considered.
In certain embodiments of the present invention, the refilling volume (V_refill) is obtained by means of the following equation (which is below also addressed as equation (7)):
      V          _      ⁢                          ⁢      refill        =            a      *      UFV        +          b      *              UFR                  hb                      _            ⁢                                                  ⁢            start                                +          c      *      OH        +    d  
In this equation, UFV, UFR and OH represent the ultrafiltration volume, the ultrafiltration rate and the overhydration level as used herein. “hb_start” is the concentration of hemoglobin in blood or any other suitable body fluid or tissue before or at the start of the treatment session, for example right after the start of the treatment.
In certain embodiments according to the present invention, parameter a equals 0.6015, b equals 0.0097, c equals 0.0223 and d equals 0.0442.
In some embodiments according to the present invention, one or more of a, b, c and d may be a negative value. In certain embodiments according to the present invention, one or more of a, b, c and d may equal zero.
Although the above noted values for a, b, c and d have been found to be helpful by the inventors to the present invention, the use of above equation is of course not limited thereto. Deviation in the values chosen for a, b, c and/or d are of course possible and also contemplated.
Of course, the equation given above may also be stated differently. As is obvious, it may have another structure as well, such as V_refill=a*UFV/Hb+b*OH+ . . . or the like.
In some embodiments, the refilling volume summed or added up over the whole treatment session may be calculated or approximated. In certain embodiments, values for the refilling volume may be calculated or approximated for certain time points. In the latter case, refilling volume values of interest may be obtained from, e. g., an exponential or exponential like extrapolation or intrapolation.
In some embodiments according to present invention, an end value of the relative blood volume arrived at an end of a blood treatment session without having caused intradialytic morbid events such as hypotonic episodes, crisis, collapse, convulsions, vomiting, sickness, nausea, or the like is predicted.
A hypotonic episode, or crisis, is in certain embodiments of the present invention defined as a subjectively felt indisposition related to low blood pressure or more or less sudden occurring blood pressure drop.
In some embodiments according to the present invention, a hypotonic episode, crisis, or collapse, is defined as a drop in blood pressure that exceeds a decrease of, e. g., 30 mmHg from the systolic blood pressure measured before or at the beginning of the treatment session (or another defined or predefined decrease in mmHg).
In certain embodiments according to the present invention, a hypotonic episode, crisis or collapse, is defined as an episode of the patient that requires medical assistance such as bringing the patient in a different posture, or stopping of the ultrafiltration, or supplying infusion of, e. g., NaCl, or the like.
In certain embodiments of the present invention, the method encompasses the step of controlling a blood treatment apparatus based on the relative blood volume calculated or approximated by means of the method according to the present invention. Similarly, in some embodiments of the present invention, the method encompasses the step of controlling a blood treatment apparatus based on the end value of the relative blood volume calculated or approximated or predicted by means of the method according to the present invention.
In certain embodiments of the present invention, the method encompasses the step of calculating or optimizing the treatment duration or the time a certain future blood treatment session lasts. The calculation or optimization is done by taking the relative blood volume or the end value of the relative blood volume into account that was gained from the method according to the present invention.
In some embodiments according to present invention, the method encompasses the step of correcting the relative blood volume by means of the patient's overhydration level—or under consideration thereof—to be a normalized or normohydrated relative blood volume (RBV_normohyd).
In certain embodiments of the present invention, the method encompasses the step of determining a target range of the relative blood volume intended to be met by the blood treatment at the end of a treatment session.
In some embodiments of the present invention, the apparatus is a controller or any (other) type of a computer.
In many embodiments of the present invention, the apparatus comprises corresponding devices such as one or more processor(s) for carrying out the method according to the present invention. The devices are adapted and/or configured for carrying out the respective method steps.
In certain embodiments of the present invention, the apparatus is or comprises a monitor.
In some embodiments of the present invention, the apparatus is configured to carry out the method according to any embodiment of the present invention.
In certain embodiments of the present invention, the apparatus comprises an output device for outputting results provided by carrying out the respective method.
In some embodiments of the present invention, the apparatus is configured to control a device for treating a patient's blood in relation to a value or target range representing the relative blood volume calculated or approximated or predicted by a method according to the present invention.
In certain embodiments, the control is such that the treatment session is terminated or interrupted—or the ultrafiltration rate (UFR) is adjusted such that the absolute blood volume or the relative blood volume (RBV) does not drop below a certain or predetermined value—once a calculated or approximated value or target range representing the relative blood volume is achieved or met by the treatment.
In some embodiments of the present invention, the apparatus is configured to control a device for treating a patient's blood such that the treatment session is terminated or interrupted once an end value of the relative blood volume is measured or calculated that has been predicted as an end value or target range of the relative blood volume. This may be a relative blood volume end value or target range that has been achieved or met without suffering any hypotonic episodes on the patient's part.
In certain embodiments of the present invention, the device according to the present invention is intended for treating a patient by means of dialysis.
In some embodiments according to the present invention, the device for treatment a patient is a machine for treating by means of hemofiltration, ultrafiltration, and/or hemodialysis.
In certain embodiments of the present invention, the apparatus is configured to control a device for treating a patient's blood such that the treatment session is terminated or interrupted once a threshold or a predetermined value of the patient's absolute blood volume has been detected or calculated.
In some embodiments according to the present invention the patient's absolute blood volume is determined during the blood treatment session by taking the relative blood volume determined during the blood treatment session into account.
In certain embodiments according to the present invention, the overhydration level is approximated, calculated or defined based on measured values and/or calculations reflecting the overhydration or the relative overhydration (relOH: overhydration (OH) over extracellular water (ECW)), etc. of the patient. As regards a definition of overhydration as used in certain embodiments of the present invention it is referred to WO 2006/002685 A1 where OH equals a*ECW+b*ICW+c*body weight. The respective disclosure of WO 2006/002685 A1 is hereby incorporated by way of reference. It is to be understood that the overhydration can be determined in different ways, all of which are known to the person skilled in the art. One of those methods comprises measuring of a dilution and calculate the overhydration based thereon.
In some embodiments according to the present invention, the overhydration level of the patient may be expressed by an age corrected overhydration or relative overhydration (relAEOH). In doing so, certain effects, e.g. due to age, can be eliminated for achieving more relevant values.
In some embodiments according to the present invention, the overhydration level of the patient is expressed by only one value, in particular a value having the dimension “liter”.
In certain embodiments according to the present invention, the overhydration level is measured or approximated before dialysis or based on pre-dialysis values of the patient.
In some embodiments according to the present invention, pre-dialysis (pre-Dx) values or calculations may be data obtained immediately, i.e., moments or minutes before starting the next dialysis treatment. The present invention is, however, not limited to this. Data can also be obtained at any other point of time. Pre-Dx data appear to be more stable than others. Using them can therefore be of advantage.
In certain embodiments according to the present invention, a target range is defined in a diagram representing both the relative blood volume and the time. The target range may alternatively be a target area. The diagram may alternatively be a plot. The diagram may be a Cartesian coordinate system, also called a “rectangular coordinate system”.
For determining the hydration or overhydration level also any appropriate monitor can be used, such as monitors based on bioimpedance or dilution techniques.
The monitor for obtaining data related to the hydration state or to the overhydration level can be a monitor as described in WO 2006/002685 A1. The respective disclosure of WO 2006/002685 A1 is hereby incorporated in the present application by way of reference. Of course, the present invention must not be understood to be limited to monitors determining the hydration state of the patient by bioimpedance measurements as is described in WO 2006/002685 A1. Other methods known in the art such as dilution measurements and also any other method known to the skilled person are also contemplated and encompassed by the present invention as well.
In some embodiments, the apparatus comprises furthermore an output device for outputting results provided by the apparatus. The output device may be a monitor having a display, a plotter, a printer or any other means for providing an output.
In certain embodiments, the hemoglobin (Hb) level, mass or concentration of the patient is calculated and/or measured. The measurement and calculations may be carried out by means of any method know in the art, using any device suitable therefor. In particular, in some embodiments, the respective data may be obtained by measuring hemoglobin concentration or mass from blood samples and/or from blood comprised in extracorporeal blood lines by means of an appropriate monitor. The measurements can be made by measuring the optical properties of the blood by optical sensors and/or by assessing acoustic properties like transit times and/or propagation velocities of ultrasonic pulses by ultrasonic sensors.
In certain embodiments, the apparatus comprises a monitor for measuring hemoglobin (Hb) concentrations (e. g., in [g/dl]) and/or for determining the blood volume by means of any monitor as described in “Replacement of Renal Function by Dialysis” by Drukker, Parson and Maher, Kluwer Academic Publisher, 5th edition, 2004, Dordrecht, The Netherlands, on pages 397 to 401 (“Hemodialysis machines and monitors”), the respective disclosure of which is hereby incorporated by way of reference.
In some embodiments, the monitor is configured to measure the blood volume and/or the concentration of hemoglobin by means of measuring an electrical conductivity.
In certain embodiments, the monitor is configured to measure the blood volume and/or the concentration of hemoglobin by means of measuring an optical density.
In some embodiments, the apparatus is configured to measure the blood volume and/or the concentration of hemoglobin by means of measuring a viscosity.
In certain embodiments, the apparatus is configured to measure the blood volume and/or the concentration of hemoglobin by means of measuring a density.
In some embodiments, the apparatus comprises one or more corresponding probes and/or one or more sensors for carrying out the measurements such as electrical conductivity sensors, optical sensors, viscosity sensors, density sensors, and the like.
In certain embodiments, the device may be used for treating a patient by means of dialysis.
In particular embodiments, the device may be used for treating a patient (or the patient's blood) by hemofiltration, ultrafiltration, hemodialysis, etc.
The embodiments may provide one or more of the following advantages.
By means of the present invention, an end value for the relative blood volume that will most probably be tolerated by the patient without severe blood pressure drops, blood pressure crisis, or collapse (the latter also being referred to as morbid events herein) may be determined in advance or early during the treatment (e. g., if the knowledge of an initial or start Hb concentration is needed, a value that can be obtained only (shortly) after the treatment has been started) of the treatment session. This may provide for the possibility to control the dialysis machine based on a reliably predicted (RBV) basis. Hence, the (critical) relative blood volume calculated or predicted in advance can be advantageously be used as a target value for the relative blood volume. The dialysis machine can be controlled accordingly. For example, the machine can be programmed to stop ultrafiltration once the (critical) relative blood volume calculated or predicted has been determined or reached or to adjust the UFR in such a way that the target RBV is not under-run.
Further, in certain embodiments, the dialysis time or duration may advantageously be optimized in certain embodiments of the present invention, because being aware in advance of a predicted relative blood volume that will most probably be tolerated by the particular patient allows controlling the dialysis machine such that the predicted relative blood volume is achieved as quickly as requested by the circumstances.
Also, once the relative blood volume predicted in advance is reached, the dialysis procedure may be stopped since further ultrafiltration may appear to be neither needed nor recommended.
Further, for optimization of the dialysis time, the control described herein ensures in certain embodiments that a predetermined ultrafiltration volume is withdrawn from the patient within a minimal or optimal time.
Further, an ultrafiltration rate may be set once the duration of the dialysis has been set and the relative blood volume or the critical relative blood volume has been predicted or calculated by means of the present invention. The so determined ultrafiltration rate will not cause a severe drop in blood pressure (crisis, collapse, or the like).
Another advantage may be that the individual refilling properties of the patient in question can be assessed once the particular refilling volume is known. The refilling volume may be calculated as described above with respect to the present invention. An assessment of the individual refilling volume may contribute to discovering certain diseases or defects of the patient regarding his or her capillary conditions (e. g., the presence of a capillary leak syndrome); it may help to check the osmotic pressure (albumin concentration), and the like. Also, assessing of the individual refilling volume may allow for providing a more individual dialysis treatment. For example, the duration of the dialysis—which can at least partly be derived from refilling volume—may be adapted to the patient's particular needs. In any way, knowing the patient's refilling volume particularities may help to further adapt the treatment to the patient's particular needs.
Moreover, by adequate use of the equations shown above, the overhydration level expected for the beginning of the next treatment session may be estimated.
Hence, the method, the apparatus and further devices according to the present invention may advantageously solve the technical problem that is how to automatically stop an automatic blood treatment before the patient starts to suffer or feel uneasy. Another technical problem that may be advantageously solved by means of the present invention is how to shorten the time the blood treatment apparatus is needed for the treatment of the patient while achieving the intended or request removal of excess fluid (or overhydration).